Medical testing device with calibrated indicia

ABSTRACT

A disposable medical testing device (17) adapted to be held against the skin of a patient, which enables the performance of skin testing for the diagnosis of both immediate hypersensitivity and delayed hypersensitivity immune reactions. The device is comprised of a hollow body with a sealed chamber in which is mounted a movable needle (3) capable of penetrating a patient&#39;s skin to a predetermined depth and a test reagent container (2). The device (17) is manipulable by a user to reduce the volume of the chamber and moving the needle thus releasing the reagent and causing penetration of the skin. The released reagent is delivered to the skin penetration site, and any resulting skin reaction is observed and recorded. Embodiments of the invention marked with a calibrated scale on a releasable transparent layer and details of patient and test date which allow multiple antigen tests to be performed are also disclosed. A method of testing for immune response using the device (17) is also disclosed.

TECHNICAL FIELD

The present invention relates to a novel disposable testing device forskin testing human subjects for immediate hypersensitivity (allergic) ordelayed hypersensitivity (cell-mediated) immune reactions. The testingdevice comprises one or more separate needles each in combination with asmall reservoir of antigen test reagent in a strip, sheet or patchformat.

BACKGROUND ART

Skin testing for allergy has conventionally been performed by putting asmall drop of the suspected allergen on the back or the forearm of thesubject and then exposing the underlying tissue by pricking the skinwith a needle. An inflammatory response occurring within about 10-15minutes indicates allergy to the suspected substance. Commonly, allergyto between 5 and 20 suspected substances may be tested in this way atany one time. This test commonly called the "skin-prick test", hasremained essentially unchanged in its design since it was firstintroduced over 70 years ago. The method, still widely used byspecialists in the field of allergic disease, is not as popular withgeneral practitioners since it takes up valuable consultation time inthe surgery, is uncomfortable for the subject and is costly to provide,especially if it is only done occasionally. Prick testing also requiressome technical skill and is quite labour intensive. However, it is themost reliable method of those used to diagnose allergy and gives aresult within 10 to 30 minutes of starting the test.

In a similar manner, testing for cell-mediated immunity may be performedby either injecting a small quantity of antigen under the surface of theskin using a needle and syringe or by puncturing the skin and allowingantigen solution to passively infiltrate the puncture site. The skinreaction, which is an index of the patient's ability to mount an immuneresponse to the test antigen, is usually measured many hours to severaldays later.

In the last 15 years, an alternative method of testing for allergy usingan in vitro assay has been introduced. The assay requires the use ofserum, the reagents used are costly, assays are only performed byspecialist pathology laboratories, and several days may elapse before aresult is known. Because of the cost, the number of tests which can beperformed is often limited to 4 suspected allergens. Only in rarecircumstances do such in vitro assays offer any advantages over skintests, for example where the skin of a patient with eczema is highlyinflamed, or when the patient is taking a particular drug whichinterferes with the skin test response. The correlation between resultsfrom skin prick tests and in vitro tests is only about 70% and there areseveral reasons why such in vitro tests sometimes produce false negativeand false positive reactions. Despite this, these assays are verypopular (well over 100 million have been performed internationally), anddespite several more companies entering the field recently and theintroduction of minor changes in design and/or procedure, no majorimprovements have been made.

It would be desirable to adapt the skin test to make it more availableand acceptable to both patient and physician, and to improve the speedand reliability of the diagnosis of immune-mediated responses. Reductionof the costs of both tests would also, of course, be welcome.

An object of the present invention is to refine the existing methods ofskin testing for the diagnosis of both immediate and delayed immunereactions. The procedure when the device of the present invention isemployed does not require any specialized technical expertise and issufficiently simple to be used, without specialised training, by generalpractitioners (GPs). It is also more acceptable to patients than whenconducted according to prior art techniques.

DISCLOSURE OF THE INVENTION

In accordance with the present invention there is provided a medicaltesting device adapted to be held against the skin of a patient toperform a test, said device comprising a hollow body providing a sealedchamber, a needle mounted within said chamber and movable to extendbeyond said body to penetrate a patient's skin to a predetermined depth,a test reagent within said chamber, and wherein said device ismanipulable by a user to reduce the volume of said chamber to releasesaid reagent and to cause penetration of said needle by moving theneedle to extend beyond said body.

In another aspect, the invention provides a method of testing for animmune response, which method comprises applying to the skin of apatient a medical testing device adapted to be held against the skin,said device comprising a hollow body providing a sealed chamber, aneedle mounted within said chamber and movable to extend beyond saidbody to penetrate a patient's skin to a predetermined depth, a testreagent within said chamber, and wherein said device is manipulable by auser to reduce the volume of said chamber to release said reagent and tocause penetration of said needle by moving the needle to extend beyondsaid body, manipulating said device to release said reagent on to theskin and to cause penetration of the skin by said needle, observing andrecording any skin reaction resulting therefrom after an appropriatetime interval.

Generally, the needle will be adapted to penetrate the skin about 1 to 2mm and may have a plurality of points or be fluted or grooved to enhanceflow of the reagent to the skin. To limit the depth to which the needlepenetrates the skin, it may be fitted with a collar or be of enlargedcross-section beyond its point or points.

In general, the reagent will be an antigen. However, other components orother reactive compounds may be included in the reagent. Differentsubstances, or dilutions of the same substance with or without controlsubstances such as the vehicle alone, or standard solutions, such as ahistamine solution, may be tested concurrently at different skin sites,when the medical testing devices of the invention are incorporated intostrips or sheets. Individual patches, strips or sheets may bemanufactured as part of a large sheet and separated into single patches,strips or sheets prior to use. In a format where multiple tests areinvolved, sufficient distance would be allowed between individualantigen/needle units to avoid one test substance interfering with anadjacent test substance. For example, in skin testing for immediatehypersensitivity, a minimum distance between units would be about 20 mm.

The reagent may be conveniently contained within a capsule, reservoir orporous matrix or may contain an additive to form a paste or gel.

It is preferred to include a transparent layer in the device of theinvention to both identify the reagent and to record details of thetest. Thus, the transparent layer may be printed with identifiers ofboth the subject tested and of the test substances employed. It ispreferably of a material which can be written on and has calibrations toenable the size of the skin reaction to be measured. It is preferablycoated on the underside with a low-tack adhesive to secure the device tothe skin in use. The adhesive also permits the transparent strip to beaffixed to the patient's medical records.

After placement of the strip or patch on the skin, light direct fingerpressure on each unit both releases the solution containing the antigenand causes the needle to penetrate the skin to a limited depthinsufficient to draw blood. The antigen solution then infiltrates thesite of the needle puncture causing a limited exposure of theintradermal or subcutaneous tissues to the antigen. The immunologicalresponse to such exposure is determined after the appropriate time,depending on the immune response involved.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a cross section of the skin test device in accordance witha first embodiment of the invention.

FIG. 2 shows a second embodiment in cross section.

FIG. 3 shows an alternate arrangement of a needle unit applicable to theinvention and illustrated in a third embodiment.

FIGS. 3A, 3B and 3C respectively depict sectional, bottom andperspective views of the needle depicted in FIG. 3.

FIG. 4 shows a cross section of fourth embodiment of the invention.

FIG. 5 shows a fifth embodiment in cross section.

FIGS. 6, 6A, 6B, 6C show various designs of needle points which can beused in the test devices of the invention.

FIG. 7 shows the view from above of patch-like embodiments of theinvention.

FIG. 8 shows a view from above of the arrangement of a test device ofthe invention including a number of antigen testing units.

FIG. 9 is a side view of the embodiment of FIG. 8.

FIG. 10 is an exploded enlarged view of one of the antigen testing unitsof FIGS. 7, 8 and 9.

FIG. 11 shows a view from above of the transparent layer of the testdevice of FIGS. 8 and 9.

BEST MODES FOR CARRYING OUT THE INVENTION

The following description relates to preferred embodiments of theinvention as illustrated in the accompanying drawings and should not beconstrued as limiting on the claims.

The skin test device (17) of FIG. 1 is made up of an antigen supportlayer (12) containing one or more (1 illustrated) capsules (2)containing antigen solution (1). Disposed to one side of the layer (12)is a compressible layer (11) and a cover (14). The layer (11) could bemade of foam plastic, rubber or be of an air cell construction, and isadhered to support (12) and cover (14) is adhered to layer (11) by meansof high-tack adhesive (15). The compressible layer (11) keeps capsule(2) and needle (3) separate when the device (17) is not in use, andkeeps the needle above the plane of the patient's skin whenuncompressed. It can also provide a physical mattress to house thecapsule (2) and the needle (3). The cover (14) incorporates a needle (3)and ensures sterility and adds rigidity. The cover may be made of amaterial such as plastic, impregnated paper or metal foil. Its uppersurface may be colour-coded and/or printed with the name(s) of theantigen(s) and with instructions for use of the device. Alternatively,it may be decorated to render the device more acceptable to children.The needle (3) which ruptures the capsule (2) prior to the needlepenetrating the skin is provided with a collar (7) to restrict the depthof penetration of needle (3) into the skin, preferably to about 1 to 2mm, when the device (17) is in use. A transparent layer (10) and bottomcover (9) are disposed on the side of the support layer (12) oppositethe needle (3) with a hole (18) in line with the needle (3). The bottomlayer (9), seals, protects and ensures the sterility of the unit. It isremoved prior to the start of the test. The removal of this layerexposes a layer of low-tack adhesive (16), shown bonded to thetransparent layer (10). The purpose of the adhesive is to temporarilyand lightly hold the device to the surface of the skin. The adhesiveconcerned should not be strong enough to cause discomfort when thedevice is removed from the skin. Layer (10) is also secured to supportlayer (12) by means of low-tack adhesive (16). The layer could be madeof plastic, cellulose, nylon or other transparent material which can bewritten on to outline the extent of a skin reaction and to recorddetails of the subject--for example the name, unit number and date. Thislayer could also be printed with scale markings in mm to enable a skinreaction such as a wheal or flare response to be measured. Low-tackadhesive (16) permits the upper layers to be removed to allow the skinreaction to be viewed through the remaining transparent layer. When theskin reaction has fully developed, it can be measured from the scale orthe outline of the reaction can be marked on the transparent layer whichmay then be removed and kept for record purposes.

In the embodiment of FIG. 2, needle guides (8) are built into top layer(14). The needle (3) is adapted to fit guide (8) tightly by means ofcollar (7'). Needle guide (8) also locates capsule (2) of antigensolution (1) between needle (3) and hole (18) in transparent layer (10).The device is sealed by bottom cover (9). Both top cover (14) and bottomcover (9) are affixed to transparent layer (10) by low-tack adhesive(16).

FIGS. 3 and 3A illustrate a further embodiment of the invention where asin the embodiments of FIGS. 1 and 2, a transparent layer (10) is boundto bottom cover (9) and the balance of the device by low-tack adhesive(16). In the embodiment of FIGS. 3 and 3A compressive layers (11) areprovided above and below a support layer (13) which holds modifiedneedle (3') and locates needle (3') above hole (18) in transparent layer(10). Compressive layer (11b) away from the transparent layer (10) isthicker than the compressive layer (11a) adjacent transparent layer (10)and carries capsule (2) of antigen solution (1) and locates it aboveneedle (3') and hole (18). Needle (3') carries barbs (4) opposite theneedle point which enable capsule (2) to be pierced to release theantigen solution (1). The device has a top cover (14). Layers (14) and(11a) (11b) and (13) are bound together with high-tack adhesive (15).

In the embodiment of FIG. 4, the antigen solution (1) is contained in areservoir (5) so shaped to correspond with a hub (19) in needle (3).Needle (3) has a hollow shaft (20) through which the antigen solution(1) can flow from the reservoir (5) to the skin test site. Needle (3)and reservoir (5) are surrounded by compressible layer (11) and coveredby a top covering layer (14). The needle and reservoir are aligned overa hole (18) in transparent layer (10) which is bound to the compressiblelayer (11) and to bottom cover layer (9) by low-tack adhesive (16).

FIG. 5 illustrates an embodiment of the invention similar to thatdescribed in FIG. 1. In the device of FIG. 5, a compressible porousmatrix (6), such as glass fibre or plastic foam, containing the antigensolution replaces the capsule (2) and collar (7) of FIG. 1. As thecapsule (1) is absent, the support layer (12) of FIG. 1 is not requiredin the embodiment described in FIG. 5.

FIG. 6 shows alternative needle configurations which may be used in theskin test device, to enhance the delivery of antigen to the skin. (A)depicts a needle with a grooved shaft, (B) depicts a needle with twinpoints, (C) depicts a needle with multiple points.

FIG. 7 depicts a preferred embodiment of the individual skin test unitscontaining the same single antigen solution arranged in a sheet form, sothat the single units can be individually separated.

The units of FIG. 7 are illustrated in more detail in FIG. 10. Theantigen solution (1) is contained within a reservoir into which theneedle (3) projects. The top covering layer (14) which could be made ofa flexible material such as an ionomer resin, e.g., Surlyn (RegisteredTrade Mark) is domed at (14') to provide the space which the needle (3)and reservoir (5) occupy. A transparent layer (10) is provided adjacentthe reservoir and has a hole (18) to permit the antigen solution toreach the skin when the device is in use. The device is sealed with abottom layer (9).

FIG. 8 illustrates a preferred embodiment of the invention wheremultiple antigen tests can be performed at the same time. A side view ofthe embodiment of FIG. 8 is illustrated in FIG. 9.

FIG. 11 shows greater detail of the transparent layer shown in theprevious figures, for the format of the skin test units shown in FIG. 8.The embodiment illustrated is marked with a callibrated scale, enablinga skin reaction response to be recorded on this layer along with detailsof the subject or patient and test date.

The volume of antigen associated with each unit is sufficient for asingle test. The aqueous solution of the antigen may contain componentsother than the antigen itself. Such components may be added, forexample, to increase the stability of the antigen, reduce thenon-specific binding of the antigen to surfaces, maintain solubility,reduce evaporation, protect against contamination by microorganisms oras a buffer. Examples of such added substances include ionic salts,non-reactive carrier proteins such as human serum albumin, non-ionicdetergents, glycerol and anti-bacterial and anti-fungal agents.

The needle is to be constructed of a material to ensure sharpness, allowsterilisation and be easily manufactured. Some examples of suchmaterials may be hard plastic, steel and nylon. The needle may penetratethe skin with a single point or may possess several points and may alsocontain features, such as fluting or grooves to improve the flow of theantigen solution into the puncture site.

The application of this design may not be restricted to in vivo testingof the immune response to antigens. Another application of this devicecould be the delivery of biological or non-biological material into theskin for purposes other than for diagnosis. Such material could be ofmicrobiological origin to function as a vaccine, immunoreactive materialto stimulate an immune response, or a therapeutic drug or othersubstance. This type of application may require minor modification tothe needle. For example, the needle in FIG. 4 would have the outletlower down the shaft towards the point to force more antigen into thepuncture site rather than as shown, where the needle is designed toflood the site allowing passive infiltration.

It may also be preferred to incorporate into the layer in contact withthe skin, as well as the weak adhesive, an absorbent band betweenantigen reservoir sites, so that excess antigen solution is not forcedfrom one test site to an adjacent site giving rise to false positivereactions.

It may also be preferred to incorporate into the layer in contact withthe skin a mild, topical, local anaesthetic which would not interferewith the skin test response, but would reduce the itching and minordiscomfort associated with an immediate skin test reaction.

Gamma irradiation may be used for sterilisation of the devices of theinvention.

INDUSTRIAL APPLICABILITY

Medical devices of the invention enable allergy and other skin tests tobe readily performed by medical and paramedical personnel to provide aquick result and permanent record.

We claim:
 1. A medical testing device adapted to be held against theskin of a patient to perform a test, said device comprising:a hollowbody having wall means defining a sealed chamber containing a testreagent therein, a releasably attachable transparent layer releasablyconnected to the body and including calibrated indicia to enable a testresult to be measured, said transparent layer forming a skin engagingsurface of the device and, in use, being located against the patient'sskin, a needle connected to said hollow body and being located withinthe body, said needle having at least one point extending toward saidtransparent layer and being moveable to extend beyond said body topenetrate the patient's skin to a predetermined depth, said device beingadapted to be depressible by a user to cause the needle to penetratesaid wall means of said chamber and release said reagent therefrom, saidpoint extending beyond said transparent layer into the patient's skin tosaid predetermined depth to cause said reagent to flow thereto.
 2. Thedevice according to claim 1, further comprising a bottom cover removablyaffixed to said transparent layer.
 3. The device according to claim 1,wherein said needle has a plurality of points facing, in use, saidtransparent layer, to enhance flow of the reagent to the skin.
 4. Thedevice according to claim 1, wherein said needle is fluted to enhanceflow of the reagent to the skin.
 5. The device according to claim 1,wherein said needle is grooved to enhance flow of the reagent to theskin.
 6. The device according to claim 1, wherein the cross section ofthe needle is enlarged to prevent penetration of the skin beyond thepredetermined depth.
 7. The device according to claim 1, wherein thetest reagent is an antigen.
 8. The device according to claim 1, whereinthe test reagent further contains a stabilizer.
 9. The device accordingto claim 1, wherein the test reagent further contains a preservative.10. The device according to claim 1, wherein the test reagent furthercontains a buffer.
 11. The device according to claim 1, wherein the testreagent is contained within a capsule or reservoir disposed within thehollow body.
 12. The device according to claim 11, wherein the needle isprovided with at least one further point facing in a direction oppositesaid point facing said transparent layer and the capsule is locatedadjacent the further point or points.
 13. The device according to claim1, wherein the test reagent is contained within a porous matrix.
 14. Thedevice according to claim 1, wherein the test reagent contains anadditive to form a paste.
 15. The device according to claim 1, whereinthe test reagent contains an additive to form a gel.
 16. The deviceaccording to claim 1, wherein the transparent layer has a surfacecapable of being written on so that the result of the test can berecorded thereon.
 17. The device according to claim 1, wherein the bodyof the device is provided with a structure deformable to reduce thevolume of said chamber.
 18. The device according to claim 11, wherein acollapsible layer is provided within said body and surrounding saidcapsule or reservoir which permits the volume of the chamber to bereduced on application of pressure to the device.
 19. A medical testingdevice comprising at least one of a strip or sheet containing aplurality of testing devices, each device comprising:a hollow bodyhaving wall means defining a sealed chamber containing a test reagenttherein, a releasably attachable transparent layer releasably connectedto the body and including calibrated indicia to enable a test result tobe measured, said transparent layer forming a skin engaging surface ofthe device and, in use, being located against the patient's skin, aneedle connected to said hollow body and being located within the body,said needle having at least one point extending toward said transparentlayer and being moveable to extend beyond said body to penetrate thepatient's skin to a predetermined depth, said device being adapted to bedepressible by a user to cause the needle to penetrate said wall meansof said chamber and release said reagent therefrom, said point extendingbeyond said transparent layer into the patient's skin to saidpredetermined depth to cause said reagent to flow thereto, each of saiddevices containing a different test reagent in its associated sealedchamber.
 20. A medical testing device adapted to be held against theskin of a patient to perform a test, said device comprising:a hollowbody containing a test reagent therein, a releasably attachabletransparent layer releasably connected to the body and includingcalibrated indicia to enable the test result to be measured, saidtransparent layer forming a skin engaging surface of the device andwhich, in use, is located against the skin of the patient, a needlelocated within the hollow body and coated by said test reagent, saidneedle having at least one point facing said transparent layer and beingmoveable to extend beyond said body to penetrate the patient's skin to apredetermined depth, and wherein said device is adapted to bedepressible by a user to cause said point to extend beyond saidtransparent layer and penetrate into the patient's skin to apredetermined depth and to cause said reagent to flow thereto.
 21. Amethod of testing for an immune response with a medical testing deviceincluding a hollow body having wall means defining a sealed chambercontaining a test reagent therein, a releasably attachable transparentlayer connected to the body and including calibrated indicia to enable atest result to be measured, a needle connected to the body and beinglocated within the device, said needle having a least one point facingthe transparent layer of the device, comprising the steps of:(a)attaching the device to the patient's skin by affixing the releasablyattachable transparent layer against the skin; (b) manipulating saidneedle so that it penetrates the sealed chamber and extends beyond thebody and transparent layer to penetrate the patient's skin, said needleby penetrating the wall means of the chamber causing reagent to bereleased therefrom through the transparent layer and into the patient'sskin; and (c) removing the hollow body by separating it from thereleasably attachable transparent layer, said transparent layerremaining against the patient's skin.